One variant of the antibody-dependent kill is particularly pertinent to the immune-mediated destruction of tumors in vivo. Animals bearing tumors of quite large size (i.e., up to 10[unreadable]9[unreadable] cells) can be effectively destroyed by the systemic administration of antitumor antibodies (particularly of the IgG[unreadable]2a[unreadable] isotype). In three distinct models, we have found that the limiting variables in such destruction are the number of macrophages within the tumor bed activated for the slow variant of ADCC. One of these models is of particular interest because it involves the destruction of established syngeneic tumors invading the tissues. Studies over the coming years are aimed at understanding lysis in molecular terms, studying the cell biology that leads to effective recognition, and analyzing how we can regulate macrophage activation more appropriately to cause increased destruction of tumors in the tissues. (MB)